Pyro-catalysis for tooth whitening via oral temperature fluctuation

Tooth whitening has recently become one of the most popular aesthetic dentistry procedures. Beyond classic hydrogen peroxide-based whitening agents, photo-catalysts and piezo-catalysts have been demonstrated for non-destructive on-demand tooth whitening. However, their usage has been challenged due to the relatively limited physical stimuli of light irradiation and ultrasonic mechanical vibration. To address this challenge, we report here a non-destructive and convenient tooth whitening strategy based on the pyro-catalysis effect, realized via ubiquitous oral motion-induced temperature fluctuations. Degradation of organic dyes via pyro-catalysis is performed under cooling/heating cycling to simulate natural temperature fluctuations associated with intake and speech. Teeth stained by habitual beverages and flavorings can be whitened by the pyroelectric particles-embedded hydrogel under a small surrounding temperature fluctuation. Furthermore, the pyro-catalysis-based tooth whitening procedure exhibits a therapeutic biosafety and sustainability. In view of the exemplary demonstration, the most prevalent oral temperature fluctuation will enable the pyro-catalysis-based tooth whitening strategy to have tremendous potential for practical applications.

In this manuscript (NCOMMS-21-29906A-Z), titled by "Pyro-catalysis for tooth whitening via oral temperature fluctuation" by Prof. Wang and etc., pyroelectricity was used for pyrocatalytic tooth whitening. Obviously, it is an interesting and novel work. However, there are lots of issues needed to be claimed before accepted by Nature Communications, which were listed as follows: 1.What's the mechanism of action of H2O2 in the Supplementary Fig.2? The pyrocatalysis becomes obvious with the addition of H2O2, is it due to the synergistic effect of pyrocatalysis and Fentonlike catalytic oxidation reaction?
2.It seems that the similar pyrocatalytic degradation of PMN-PT in Supplementary Fig. 4, which was previously mentioned in the supplementary materials of Nat. Commun. 9, 1-8 (2018). Therefore, it had better delete Supplementary Fig. 4. 3.The two videos are the cold-hot setup and the infra-imaging of drinking cold and hot water, respectively. Please provide the videos of obvious pyrocatalysis experiment displayed the results in the manuscript? 4.In the Fig. 3 and Supplementary Fig. 6 and 7, the unit of magnetic field should be "Gs", not "G". The different cycling times exhibiting different curves should be labeled in the Supplementary Fig.  6.
5.The pyroelectric performance of poled and unpoled BaTiO3 catalyst should be provided in this work.
6.In the equation 1, the multiplication "·" should be added between these physical quantities.
7.What's the final product of the organic matter on the tooth after pyrocatalytic whitening? Decolorization, decomposition or degradation? It's better to do the TOC measurement. This manuscript aimed at to study a novel tooth-whitening strategy based on pyroelectric material (BaTiO3 hydrogel)-decorated braces as well as the impact of oral temperature fluctuations. And the resultant BaTiO3 nanowires exhibited satisfactory pyro-catalytic activities for the degradation of Indigo Carmine pollutants at different temperature ranges. Interestingly, a self-made dental brace with BaTiO3 hydrogel could significantly whiten teeth while exhibiting remarkably therapeutic biosafety and sustainability. This work revealed the practical application potential of pyroelectric materials in the field of tooth whitening. It's reasonable from the view of technique. Following issues can be considered to make this work better: Specific comments are presented as follows: 1. In Introduction, more research developments on the application of the host material BaTiO3 in pyroelectric-catalysis should be added. 2. In section "Indigo Carmine degradation based on pyro-catalysis", It says that "17 thermal cycles were required for a 95% degradation of Indigo Carmine at 26-36 °C (ΔT= -10 °C), while only 6 thermal cycles were required for the same degradation of Indigo Carmine at 36-46 °C (ΔT= 10 °C)." This result is not reflected in Supplementary Fig. 4. 3. P11, the fifth line in the third paragraph, "The total charges induced by the pyroelectricity …… at a rapid heating rate.", thereinto, how to reflect the charge recombination and release efficiency caused by pyroelectricity? It can be further discussed.

Dear Dr. Robert Guilliatt and referees,
We are truly grateful to your critical comments and thoughtful suggestions. Based on these comments and suggestions, we have made careful modifications on the original manuscript. All changes made to the text are in red color. We hope the new manuscript will meet your journal's standard. Below you will find our point-by-point responses to the reviewers' comments/questions below:

Reviewer #1
In this manuscript (NCOMMS-21-29906A-Z), titled by "Pyro-catalysis for tooth whitening via oral temperature fluctuation" by Prof. Wang and etc., pyroelectricity was used for pyrocatalytic tooth whitening. Obviously, it is an interesting and novel work.
However, there are lots of issues needed to be claimed before accepted by Nature Communications, which were listed as follows: 1.What's the mechanism of action of H2O2 in the Supplementary Fig.2? The pyrocatalysis becomes obvious with the addition of H2O2, is it due to the synergistic effect of pyrocatalysis and Fenton-like catalytic oxidation reaction?
2.It seems that the similar pyrocatalytic degradation of PMN-PT in Supplementary Fig.   4, which was previously mentioned in the supplementary materials of Nat. Commun. 9, 1-8 (2018). Therefore, it had better delete Supplementary Fig. 4. 3.The two videos are the cold-hot setup and the infra-imaging of drinking cold and hot water, respectively. Please provide the videos of obvious pyrocatalysis experiment displayed the results in the manuscript? 4.In the Fig. 3 and Supplementary Fig. 6 and 7, the unit of magnetic field should be "Gs", not "G". The different cycling times exhibiting different curves should be labeled in the Supplementary Fig. 6. 5.The pyroelectric performance of poled and unpoled BaTiO3 catalyst should be provided in this work.
6.In the equation 1, the multiplication "·" should be added between these physical quantities.
7.What's the final product of the organic matter on the tooth after pyrocatalytic whitening? Decolorization, decomposition or degradation? It's better to do the TOC measurement.
8.Please provided the scale line mark of the morphology characterization in Fig. 2. 9.Is the nanowire BTO broken in the pyrocatlytic experiments? Please provide the comparation before and after pyrocatalysis with the different microstructure and morphology of BTO catalyst.
10.How about the effect of the size and shape of BTO catalyst on the pyrocatalysis? Comment 1: What's the mechanism of action of H2O2 in the Supplementary Fig.2?
The pyrocatalysis becomes obvious with the addition of H2O2, is it due to the synergistic effect of pyrocatalysis and Fenton-like catalytic oxidation reaction?
Response: Thank you for this comment. It is clear that the addition of H2O2 significantly accelerated the degradation of indigo carmine based on the experimental results. It has been shown that hydrogen peroxide is involved in the catalytic process as an intermediate product in photocatalysis (see Fig.1 in response letter), and the addition of hydrogen peroxide to the reaction system can induce a Fenton-like effect to enhance the catalytic rate for photocatalysis.  (Applied Catalysis B: Environmental, 2020, 272: 118970.) Analogous to the photocatalysis, we designed experiment to clarify the mechanism of action of H2O2 ( Supplementary Fig. 3). We monitored the concentration of H2O2 in the solution using liquid chromatography during the pyro-catalysis process. The results show that the concentration of H2O2 did not change throughout the pyro-catalysis process ( Supplementary Fig. 3), so we concluded that there was both consumption and generation of H2O2 during the pyro-catalysis process. The added small amount of H2O2 combine with the charge released from the pyroelectric material, which then release free radicals in a Fenton-like reaction. Hence the pyro-catalysis reaction was accompanied by the generation of H2O2, thus achieving a balance between generation and consumption of H2O2.
Additionally, DPD-POD method was further employed to clarify the mechanism of action of H2O2. The related results were shown in Supplementary Fig. 4 (Page 5).
Supplementary Fig. 4 a Typical absorption spectra obtained by testing different concentrations of H2O2 using the DPD-POD method. b The linear relationship between the H2O2 concentration and the peak of the absorption spectrum at 551 nm can be used to calculate the H2O2 concentration in the unknown solution. c the absorption spectra of H2O2 concentrations created by BTO during pyro-catalysis. d The concentration of H2O2 in the reaction system with and without BTO after a specific number of thermal cycles.
H2O2 detection. The concentration of H2O2 created during pyro-catalysis process was measured by a DPD−POD method. Briefly, 50mg of BTO was dispersed in 50ml of water, and after a certain number of thermal cycles, samples of the liquid were centrifuged and 1mL of the supernatant was added to a mixture of 3 mL of phosphate buffer (0.5 M, pH = 6), 6 mL of water, 0.05 mL of N,N-diethyl-p-phenylenediamine sulfate (DPD, 10 mg mL -1 ) and 0.05 mL of peroxidase (POD, 1 mg mL -1 ). After 30 s, the H2O2 concentration was measured at 551 nm on a UV−vis spectrophotometer.
DPD-POD method was further employed to verify the role of small amount addition of H2O2 during pyro-catalysis process 1,2 . First, the linear relationship between the peak of the absorption spectrum at 551 nm and concentrations of added H2O2 indicates the validity of the DPD-POD method, as shown in Supplementary Fig. 4 a and b. It can be seen that the generation of H2O2 increase with the number of thermal cycles and about 300 μM of H2O2 was produced in the reaction system after 30 hot and cold cycles at a temperature fluctuation of +20 ℃, as shown in Supplementary Fig. 4 a and b.
The discussion can be found in main text at page 10, and we also added refs. 39 and 40.
"In contrast, the degradation of Indigo Carmine was minimal when BTO nanowires were used as catalyst or when BTO nanowires were not added ( Supplementary Fig. 2).
The concentration of H2O2 monitored by liquid chromatography shows no change during the pyro-catalysis process ( Supplementary Fig. 3), while the DPD-POD experimental results indicate the generation of 300 μM of H2O2 in the reaction system after 30 hot and cold cycles at a temperature difference of +20 ℃ (Supplementary Figs. 4). Anomalous to photo-catalysis, it can be inferred that H2O2 is as an intermediate product and remains an equilibrium state between consumption and generation during the pyro-catalysis process. The charges released from the pyro-catalytic BTO nanowires was first combined with the addition of H2O2, and subsequently react further into reactive radicals in a Fenton-like reaction 39,40 . The addition of small amount of H2O2 can accelerate the pyro-catalytic process and improve the efficiency. These comparative experiments unambiguously verify that the degradation of Indigo Carmine due to the catalysis effect is strongly associated with the pyroelectricity of the nanowires." Comment 2: It seems that the similar pyrocatalytic degradation of PMN-PT in Supplementary Fig. 4, which was previously mentioned in the supplementary materials of Nat. Commun. 9, 1-8 (2018). Therefore, it had better delete Supplementary Fig. 4.

Response:
Thank you for your suggestion. It is true that, as you mentioned, PMN-PT has been used to demonstrate pyro-catalysis effect in previous publications, but in this work, the pyro-catalytic degradation of indigo carmine by PMN-PT can effectively illustrate the relationship between pyro-catalysis effect and pyroelectric coefficient, and moreover, the supplementary results are consistent with the data in Supplementary "PMN-PT single crystal powder with high pyroelectric properties was used for comparative pyro-catalytic degradation experiments. Single crystals were first crushed and then poled using corona poling method 3 . The same degradation of indigo carmine using PMN-PT powders were performed as BTO nanowires at different temperature fluctuation. The results show that PMN-PT single crystal powder required fewer thermal cycles and the organic dyes can be degraded more completely, which is consistent with previous reports 4 ." Comment 3: The two videos are the cold-hot setup and the infra-imaging of drinking cold and hot water, respectively. Please provide the videos of obvious pyrocatalysis experiment displayed the results in the manuscript?
Response: Thank you for this suggestion. We have provided a typical video of the entire process of degrading indigo carmine with BTO nanowires in Supplementary Video 1, and the corresponding text is in page 10: "Impressively, at temperature fluctuation of ΔT= 20 ℃, only three thermal cycles are required to degrade the Indigo Carmine (Supplementary Video 1)." Comment 4: In the Fig. 3 and Supplementary Fig. 6 and 7, the unit of magnetic field should be "Gs", not "G". The different cycling times exhibiting different curves should be labeled in the Supplementary Fig. 6.
Response: Thanks a lot for your careful review, the units in the Fig. 3, Fig. 5, Supplementary Fig. 9 and Supplementary Fig. 10 has been carefully checked and modified, and a specific number of cycles was added to Supplementary Fig. 9 and Supplementary Fig. 10 to obtain a more intuitive result.
In the main text on page 9
In the main text on page 16  Fig. 15. It can be seen the pyro-catalytic performance of the poled BTO nanowires was decreased related to the unpoled BTO nanowires (or as-grown). It is highly possible that the as-grown BTO nanowires are mainly along the [001] direction, which is the highest pyroelectric coefficient direction for the tetragonal BTO. The grown nanowires have highly self-poled along the length direction. However, after being poled using an applied electric field, the polarization along the length direction was disrupted and rearranged leading to a decrease of pyroelectric properties. The same experiment was carried out using PMN-PT single crystal powder. In contrast to BTO nanowires, the catalytic performance of PMN-PT powder after poling was greatly improved for PMN-PT powder with randomly distributed polarization direction. These comparative experiments unambiguous verify that the pyro-catalysis performance is determined by the pyroelectricity (or degree of polarization), which is similar to the piezo-catalysis 3 . Response: Thank you for your careful examine. In the main text on page 11. The equation 1 has been changed into

ΔQ=p·A·ΔT
(1) Comment 7: What's the final product of the organic matter on the tooth after pyrocatalytic whitening? Decolorization, decomposition or degradation? It's better to do the TOC measurement.
Response: Thank you for your critical suggestion. Since it is very difficult to test the change in the total amount of organic matter on the tooth surface during the catalytic process, and the exogenous staining of teeth mainly comes from pigments in food, we aimed our tests at the degradation process of indigo carmine solution. TOC measurement was performed to determine the change of total organic matter in the indigo carmine solution during the catalytic process ( Supplementary Fig. 8). The results show that the TOC value in the solution decreased throughout the catalytic process, indicating that the organic matter in the solution decreased and was converted into CO2 and H2O. Thus, it can be inferred that the organic matter on the tooth surface was degraded rather than discolored or decomposed during the tooth whitening process. The related discussion on the TOC experiment can be found in the main text on page 12.
"Total organic carbon (TOC) measurement was performed to monitor the total amount of organic carbon in the Indigo Carmine degradation experiment. As the reduction of TOC reflects the extent of degradation or mineralization of an organic species, the TOC value in the pyro-catalysis experiment was studied as a function of thermal cycles ( Supplementary Fig. 8). The initial TOC value of the Indigo Carmine is 39.85 mg L -1 . After 9 thermal cycles with a temperature fluctuation of +5 ℃, the TOC value decreased to 8.36 mg L -1 (i.e., ~20% of the initial TOC value). The reduction of TOC confirms that color change was due to degradation of Indigo Carmine macromolecules (Eq.5), rather than decolorization or decomposition." Comment 8: Please provided the scale line mark of the morphology characterization in Fig. 2.
Response: Thanks a lot for this careful review. We have provided a scale for each of the morphology characterization in Figure 2. In the main text on page 6.  The comparison of BTO before and after pyro-catalysis has been added as before and c after pyro-catalysis. [ACS Appl Mater Interfaces 2018, 10, 37963.]. This indicates that the effect of the size of the nanomaterials is not dominant in pyro-catalysis, but rather the pyroelectric potential that can be generated by the material dominates the rate at which the catalytic reaction proceeds.

Pyro-catalysis performance of BTO with different size and shape. [ACS Appl Mater
Interfaces 2018, 10, 37963.] The simulation results also reveal a similar conclusion. Since the BTO nanowires grow preferentially along the polar axis, the nanowires have spontaneous polarization along the length direction. The results show that the BTO nanowires exhibit superior pyroelectric properties with higher pyroelectric potential relative to nanoparticles of smaller size and larger surface area.

Pyroelectric potential of BTO nanocrystals with different morphologies. [ACS Appl
Mater Interfaces 2018, 10, 37963.] Based on the reported result, we believe that the effect of size on the performance of pyro-catalysis is minimal, and the performance of pyro-catalysis primarily depends on how much pyroelectric potential can be generated. BTO nanowires have better pyrocatalysis performance due to their spontaneous polarization along the length direction, and can generate considerable pyroelectric potential, which is an advantage relative to other morphologies. This is the main reason why we chose BTO nanowires in our experiment.

Reviewer #2:
This manuscript aimed at to study a novel tooth-whitening strategy based on pyroelectric material (BaTiO3 hydrogel)-decorated braces as well as the impact of oral temperature fluctuations. And the resultant BaTiO3 nanowires exhibited satisfactory pyro-catalytic activities for the degradation of Indigo Carmine pollutants at different temperature ranges. Interestingly, a self-made dental brace with BaTiO3 hydrogel could significantly whiten teeth while exhibiting remarkably therapeutic biosafety and sustainability. This work revealed the practical application potential of pyroelectric materials in the field of tooth whitening. It's reasonable from the view of technique.
Following issues can be considered to make this work better: Specific comments are presented as follows: 1. In Introduction, more research developments on the application of the host material BaTiO3 in pyroelectric-catalysis should be added. 3. P11, the fifth line in the third paragraph, "The total charges induced by the pyroelectricity …… at a rapid heating rate.", thereinto, how to reflect the charge recombination and release efficiency caused by pyroelectricity? It can be further discussed.

In section "Indigo
4. In this work, it was relatively scarce in the characterization and analysis of materials.
As we know, the human oral environment is complex, in addition to exploring the recyclable activity of the BaTiO3 nanowires, it is also necessary to explore the stability of the resultant material in a variety of simulated oral environments. At the same time, it is necessary to characterize and analyze the structure of the material before and after the reaction.
5. The composition of oral saliva is complex, whether there are some inorganic ions (e.g. K+, Na+, Ca+) and active enzyme species that compete for the charge generated by the pyroelectricity, disturb the trade-off between charge and ROS generation; secondly, the oral saliva contains lysozyme and thiocyanate ion that play a role in oral sterilization, whether cyanide ion can achieve the synergistic bactericidal effect with ROS in this simulated environment, it needs to be further explored.
6. What is the specific role of H2O2 in the pro-catalytic effect test? No specific explanation was given in the manuscript. In addition, we know that •O2-will be further reduced to generate H2O2. Whether H2O2 will be generated during the pyroelectriccatalysis process can be further discussed.
7. In the Fig. 5g-h, it is obvious that in addition to the EPR peak of •O2-, there are other split peaks generated, indicating the generation of other derived radical intermediates (e.g. •CH3, •CHO), which can be further explored. And it is best to supplement the corresponding mechanism study.
Comment 1: In Introduction, more research developments on the application of the host material BaTiO3 in pyroelectric-catalysis should be added.

Response:
We thank the reviewer for the suggestion. We have included the application of BTO in pyro-catalysis in the introduction section in page 3 and added refs.25-28.
"As an environmental-friendly lead-free pyroelectric material, BaTiO3 (BTO) has attracted much attention in the field of pyro-catalysis, such as dye degradation by lightinduced temperature change and waste heat 25,26,27 , and wastewater treatment with assistance of metal nanoparticles 28 ."

Comment 2:
In section "Indigo Carmine degradation based on pyro-catalysis", It says that "17 thermal cycles were required for a 95% degradation of Indigo Carmine at 26- "17 thermal cycles were required for a 95% degradation of Indigo Carmine at 26-36 ℃ (ΔT= -10 ℃), while only 6 thermal cycles were required for the same degradation of Indigo Carmine at 36-46 ℃ (ΔT= 10 ℃)." has been changed into "13 thermal cycles were required for a 95% degradation of Indigo Carmine at 26-36 ℃ (ΔT= -10 ℃), while only 6 thermal cycles were required for the same degradation of Indigo Carmine at 36-46 ℃ (ΔT= 10 ℃) ( Fig. 2a and Fig 2d)." Comment 3: P11, the fifth line in the third paragraph, "The total charges induced by the pyroelectricity …… at a rapid heating rate.", thereinto, how to reflect the charge recombination and release efficiency caused by pyroelectricity? It can be further discussed.
Response: Thank you for this critical comment. We designed a series of experiment to verify that the release of massive free charges leads to a decrease in catalytic efficiency due to the charge recombination. We have performed pyro-catalysis experiments using different catalyst concentrations under the same temperature fluctuation and temperature rise rate. There is no doubt that higher concentration of catalysts will release more charges and more radicals, if the charges do not recombine with each other.
However, it was observed that when the catalyst dosage exceeds a certain range, further increase in catalyst concentration has a negative impact on the efficiency of pyrocatalysis. We believe that this is because the simultaneous release of charges in the reaction system is too high, resulting in the recombination of charges with each other instead of reacting with water molecules to form radicals.
The added experimental results were presented in Supplementary Fig.7, and the related further discussion can be found in main text on page 12.
"In order to further discuss the charge recombination and release efficiency on cooling or heating rate, we have additionally performed pyro-catalysis experiment using different catalyst concentrations under the same temperature fluctuation (i.e., ΔT= +10 ℃) and temperature rise rate ( Supplementary Fig. 7). The pyro-catalytic efficiency increases and then decreases with the increase of catalyst concentration, indicating that charge release efficiency higher than a center degree will result in the recombination of charges with each other instead of reacting with water molecules to form radicals 42,43 ." Comment 4: In this work, it was relatively scarce in the characterization and analysis of materials. As we know, the human oral environment is complex, in addition to exploring the recyclable activity of the BaTiO3 nanowires, it is also necessary to explore the stability of the resultant material in a variety of simulated oral environments.

Supplementary
At the same time, it is necessary to characterize and analyze the structure of the material before and after the reaction.
Response: Thank you for this valuable comment. In order to verify BTO nanowires with good stability in the human oral environment, we have carried out the following work: 1) We conducted degradation experiments of indigo carmine using artificial saliva as a solvent for BTO nanowires and BTO gels, respectively. The results show that BTO nanowires still have good cyclic stability in the oral environment simulated by artificial saliva ( Supplementary Fig. 11).
2) In addition, we conducted XRD and SEM analysis of BTO nanowires after the catalytic cycling stability characterization in the artificial saliva environment ( Supplementary Fig. 12). The results show that the phase and morphology of BTO nanowires did not change before and after the catalytic test in the oral environment simulated by artificial saliva, so it is evident that the BTO nanowires have good cycling performance and stability in the human oral environment. The discussion corresponding to the results is on page 13 in the main text and Supplementary Fig. 11 and 12.
"Due to the complexity of the human oral environment resulting in saliva with many other metal ions as well as enzymes, artificial saliva was employed as a solvent for pyro-catalytic indigo carmine degradation in order to exclude the effect of saliva environmental complexity. The BTO nanowires were subjected to three cycles at a temperature fluctuation of +5 ℃. It can be seen that the BTO nanowires exhibit excellent cycling stability in the artificial saliva environment ( Supplementary Fig. 11), and their pyro-catalytic performance in this artificial saliva environment is almost the same as that in deionized water (Fig. 3c). In addition, the phase structure and morphology of the BTO nanowires themselves remains stable ( Supplementary Fig. 12).
This result provides strong support for the application of pyro-catalysis for tooth whitening" Supplementary Fig. 11 a-c UV-Vis absorption spectra of Indigo Carmine solutions with artificial saliva as solvent using the same BTO nanowires for three cycles. b Cyclic stability of BTO nanowires degraded indigo solution.
Artificial saliva ( purchased from Shanghai yuanye Bio-Technology Co., Ltd ) was used to simulate the real environment of human oral cavity, which is mainly composed of deionized water, NaCl, KCL, Na2SO4, NH4Cl, CaCl2-2H2O, NaH2PO4-2H2O, CN2H4O, NaF, and this is more than 99% similar to human saliva. After the indigo carmine was dissolved, pyro-catalytic degradation experiments were performed, and the results exhibited in Supplementary Fig. 11 Supplementary Fig. 12 a X-ray diffraction pattern of the BTO nanowires before and after pyro-catalysis, and scanning electron microscope image of BTO nanowires b before and c after pyro-catalysis.

Comment 5:
The composition of oral saliva is complex, whether there are some inorganic ions (e.g. K+, Na+, Ca+) and active enzyme species that compete for the charge generated by the pyroelectricity, disturb the trade-off between charge and ROS generation; secondly, the oral saliva contains lysozyme and thiocyanate ion that play a role in oral sterilization, whether cyanide ion can achieve the synergistic bactericidal effect with ROS in this simulated environment, it needs to be further explored.
Response: Thank you for this thoughtful comment. As you said, the real human oral environment is very complex and saliva contains many metal ions as well as enzymes.
To ensure that the BTO nanowires can generate free radicals for organic degradation in such a complex environment, we chose artificial saliva as the solvent for Indigo Carmine and performed pyro-catalysis experiments. The results showed that even in the complex environment of saliva, the excellent catalytic performance of the BTO nanowires was not affected by the flammability and showed excellent performance and structural stability. Thus, we conclude that the complexity of the oral environment does not affect the radical production of BTO nanowires. These results is included in the text on page 13 and in Supplementary Information on page 12 and 13.
"Due to the complexity of the human oral environment resulting in saliva with many other metal ions as well as enzymes, artificial saliva was employed as a solvent for pyro-catalytic indigo carmine degradation in order to exclude the effect of saliva environmental complexity. The BTO nanowires were subjected to three cycles at a temperature fluctuation of +5 ℃. It can be seen that the BTO nanowires exhibit excellent cycling stability in the artificial saliva environment ( Supplementary Fig. 11), and their pyro-catalytic performance in this artificial saliva environment is almost the same as that in deionized water (Fig. 3c). In addition, the phase structure and morphology of the BTO nanowires themselves remains stable ( Supplementary Fig. 12).
This result provides strong support for the application of pyro-catalysis for tooth whitening." Supplementary Fig. 11 a-c UV-Vis absorption spectra of Indigo Carmine solutions with artificial saliva as solvent using the same BTO nanowires for three cycles. b Cyclic stability of BTO nanowires degraded indigo solution Artificial saliva ( purchased from Shanghai yuanye Bio-Technology Co., Ltd ) was used to simulate the real environment of human oral cavity, which is mainly composed of deionized water, NaCl, KCL, Na2SO4, NH4Cl, CaCl2-2H2O, NaH2PO4-2H2O, CN2H4O, NaF, and this is more than 99% similar to human saliva. After the indigo carmine was dissolved, pyro-catalytic degradation experiments were performed.
Supplementary Fig. 12 a X-ray diffraction pattern of the BTO nanowires before and after pyro-catalysis, and scanning electron microscope image of BTO nanowires b before and c after pyro-catalysis.
In fact, we are working on the use of free radicals for sterilization, as shown in the figure below. We added BTO nanowires to the culture medium and exposed the culture environment to thermal cycles at 20-45℃. From the results of spiral plating, it can be seen that with the help of pyro-catalysis, the bacterial survival rate of the group that added BTO was significantly reduced to 30%, while the bacterial growth of the group that without BTO did not receive a significant effect. This result indicates that the reactive radicals released during pyro-catalysis can be used to achieve bactericidal activity. Based on the present results, it is speculated that the use of free radicals to achieve sterilization with the help of components in the oral environment is highly feasible. This result has been added as Supplementary Fig. 16 and can be found in page 21 in the main text. "The concepts and results strongly highlight the bright prospects of pyroelectric materials used for tooth whitening, or even oral sterilization ( Supplementary Fig. 16)." Supplementary Fig. 16 pyro-catalysis for antibacterial activity in vitro. a-b Results of spiral inoculation and c cell activity before and after pyro-catalysis.
The pyro-catalytic bacteria sterilization experiment was performed using streptococcus mutans (UA159), which is the culprit of dental plaque and tooth decay.  Fig. 16) reveal that the active radicals released by BTO nanowires through pyro-catalysis have a significant bactericidal effect with only 40% survival.
Comment 6: What is the specific role of H2O2 in the pro-catalytic effect test? No specific explanation was given in the manuscript. In addition, we know that •O2-will be further reduced to generate H2O2. Whether H2O2 will be generated during the pyroelectric-catalysis process can be further discussed.
Response: Thank you for this comment. It is clear that the addition of H2O2 significantly accelerated the degradation of indigo carmine based on the experimental results. It has been shown that hydrogen peroxide is involved in the catalytic process as an intermediate product in photocatalysis (see Fig.1 in response letter), and the addition of hydrogen peroxide to the reaction system can induce a Fenton-like effect to enhance the catalytic rate for photocatalysis. Catalysis B: Environmental, 2020, 272: 118970.) Analogous to the photocatalysis, we designed experiment to clarify the mechanism of action of H2O2 ( Supplementary Fig. 3). We monitored the concentration of H2O2 in the solution using liquid chromatography during the pyro-catalysis process. The results

Fig.1 Photocatalytic reaction mechanisms (Applied
show that the concentration of H2O2 did not change throughout the pyro-catalysis process ( Supplementary Fig. 3), so we concluded that there was both consumption and generation of H2O2 during the pyro-catalysis process. The added small amount of H2O2 combine with the charge released from the pyroelectric material, which then release free radicals in a Fenton-like reaction. Hence the pyro-catalysis reaction was accompanied by the generation of H2O2, thus achieving a balance between generation and consumption of H2O2.
Additionally, DPD-POD method was further employed to clarify the mechanism of action of H2O2. The related results were shown in Supplementary Fig. 4 (Page 5).
Supplementary Fig. 4 a Typical absorption spectra obtained by testing different concentrations of H2O2 using the DPD-POD method. b The linear relationship between the H2O2 concentration and the peak of the absorption spectrum at 551 nm can be used to calculate the H2O2 concentration in the unknown solution. c the absorption spectra of H2O2 concentrations created by BTO during pyro-catalysis. d The concentration of H2O2 in the reaction system with and without BTO after a specific number of thermal cycles.
H2O2 detection. The concentration of H2O2 created during pyro-catalysis process was measured by a DPD−POD method. Briefly, 50mg of BTO was dispersed in 50ml of water, and after a certain number of thermal cycles, samples of the liquid were centrifuged and 1mL of the supernatant was added to a mixture of 3 mL of phosphate buffer (0.5 M, pH = 6), 6 mL of water, 0.05 mL of N,N-diethyl-p-phenylenediamine sulfate (DPD, 10 mg mL -1 ) and 0.05 mL of peroxidase (POD, 1 mg mL -1 ). After 30 s, the H2O2 concentration was measured at 551 nm on a UV−vis spectrophotometer.
DPD-POD method was further employed to verify the role of small amount addition of H2O2 during pyro-catalysis process 1,2 . First, the linear relationship between the peak of the absorption spectrum at 551 nm and concentrations of added H2O2 indicates the validity of the DPD-POD method, as shown in Supplementary Fig. 4 a and b. It can be seen that the generation of H2O2 increase with the number of thermal cycles and about 300 μM of H2O2 was produced in the reaction system after 30 hot and cold cycles at a temperature fluctuation of +20 ℃, as shown in Supplementary Fig. 4 a and b.
The discussion can be found in main text at page 10, and we also added refs. 39 and 40.
"In contrast, the degradation of Indigo Carmine was minimal when BTO nanowires were used as catalyst or when BTO nanowires were not added ( Supplementary Fig. 2).
The concentration of H2O2 monitored by liquid chromatography shows no change during the pyro-catalysis process ( Supplementary Fig. 3 Response: Thank you for this comment. We carefully examined the results of the EPR spectra and there were indeed peaks in the spectra that did not belong to •O2 -. After comparing them with the literature we confirmed that the additional peaks were from •CH3. In the detection of •O2 -, DMSO is used as the solvent, and the •OH generated in the pyro-catalysis process will react with DMSO, and the •CH3 generated in the reaction will be captured by DMSO to form DMSO-•CH3. When the peak of DMSO-•O2and the peak of DMSO-CH appear at the same time, the spectrum in the text will be obtained. In the EPR spectrum of DMPO-O2 -, a typical peak belonging to DMPO-CH3 was found. This is due to the fact that DMSO is used as an OH trapping agent when testing O2 -, but at the same time, DMSO is also oxidized by OH to produce CH3 that cannot be produced by DMPO, and the reaction process can be expressed by the following equations 5,6 :

Production of DMPO-OCH3 adduct is most likely initiated by
In the revised manuscript (NCOMMS-21-29906A-Z), titled by "Pyro-catalysis for tooth whitening via oral temperature fluctuation" by Prof. Wang and etc., The issues raised by the reviewer has been answered and responded. Pyroelectricity was used for pyrocatalytic tooth whitening, and it is an interesting and novel work. In my opinion, the revised manuscript can be ccepted by Nature Communications Reviewer #2 (Remarks to the Author): After revision, the manuscript has been obviously improved. Before acceptance, some more issues are concerned.
(1) The authors have mentioned some cases that may cause oral temperature fluctuations, however, I am wondering how these cases matching the working conditions required for pyrocatalysis processes. For example, those above-mentioned cases are related to feeding and intaking, usually accompanying with tooth contamination, how would these cases are compatible with pyro-catalysis assisted tooth cleaning processes, which are otherwise associated with falling and degrading the disgusting or even hazardous contaminants from the tooth. Please try to figure out the suitable practical application scenario.
(2) Essentially, the tooth whitening by pyro-catalysis, similar to the photo-catalysis and piezocatalysis, are achieved via reactive oxidative species (ROSs), such as superoxide •O2− and •OH radicals, mediated oxidative degradation processes. I am wondering the fundamental differences between the pyro-catalysis and the others, the different generation rate of ROSs? How to understand their big difference in balancing the tooth whitening efficiency and biosafety?
(3) Why BaTiO3? Why BaTiO3 nanowires? What are the major considerations for choosing a material for tooth whitening, among the available materials? What are the major factors affecting activity of pyro-catalysts? It is strange that the activity is not significantly affected by size of pyrocatalysts, although surface area (A) is an important parameter determining the surface charge.
(4) Thermodynamically, how much energy is needed to generate ROS (equation 3/4) in pyrocatalysis? How to estimate the energy conversion efficiency in pyro-catalysis? Is the temperature change (ΔT) providing sufficient energy to activate oxygen or water molecules? (5) For oral and intake safety, in addition to the potential harms from ROSs and materials, the pyro-catalysis degradation processes and intermediates shall be also considered.
In the revised manuscript (NCOMMS-21-29906A-Z), titled by "Pyro-catalysis for tooth whitening via oral temperature fluctuation" by Prof. Wang and etc., The issues raised by the reviewer has been answered and responded. Pyroelectricity was used for pyrocatalytic tooth whitening, and it is an interesting and novel work. In my opinion, the revised manuscript can be accepted by Nature Communications.

Response:
We are grateful for the referee's positive comments.

Reviewer #2 (Remarks to the Author):
After revision, the manuscript has been obviously improved. Before acceptance, some more issues are concerned.
(1) The authors have mentioned some cases that may cause oral temperature fluctuations, however, I am wondering how these cases matching the working conditions required for pyro-catalysis processes. For example, those above-mentioned cases are related to feeding and intaking, usually accompanying with tooth contamination, how would these cases be compatible with pyro-catalysis assisted tooth cleaning processes, which are otherwise associated with falling and degrading the disgusting or even hazardous contaminants from the tooth. Please try to figure out the suitable practical application scenario.
Response: thanks a lot for this valuable comment. For tooth cleaning, the pyroelectric material could be mixed with hydrogel into dental retainers, patients wearing the retainer can achieve tooth whitening due to oral temperature fluctuations induced by various oral activities such as cold/hot beverages drinking, ice cream eating, and even speaking. However, when patients intake foods, wearing a retainer may cause difficulties for patients to masticate, and even generate hazardous contaminants from the tooth, in this case, the pyro-catalysis is not compatible. Accordingly, the application scenario in Fig. 1a has been revised, the scenario of eating hotpot is replaced with drinking hot tea in the new Fig. 1a.
Additionally, there are many other oral activities that are compatible with pyro-catalysis assisted tooth cleaning, such as closing and opening the mouth during daily conversations, and breathing during exercise. We have added these appropriate scenarios in the text.
On page 3, "Temperature fluctuations are the most prevalent stimuli in our oral environment, when the mouth is open and close during speaking, drinking, and mouth breathing during exercise. (Fig. 1a)." On page 5, "These retainers can achieve pyro-catalysis through temperature fluctuations in the mouth induced by daily oral activities (e.g., drinking, breathing, talking, exercising, etc.), without using any other assistant equipment. The generated constant stream of active radicals will attack and degrade the stains on the tooth surface." On page 21, "This strategy can be conveniently implemented during our daily oral activities (e.g., drinking, breathing, talking, exercising, etc.) without extra timeconsuming and additional equipment." The use of retainers provides excellent protection against secondary staining caused by diet, and also prevents degradation products from entering the digestive tract.
In addition, a variety of tooth whitening products with peroxide as a whitening agent already exist on the market, we believe that the degradation products of enamel stains will not cause damage to the human body as pyro-catalysis tooth whitening is mechanistically identical to commercial gels (ROS degrades colored macromolecules into small colorless molecules or H2O and CO2).
(2) Essentially, the tooth whitening by pyro-catalysis, similar to the photo-catalysis and piezo-catalysis, are achieved via reactive oxidative species (ROSs), such as superoxide •O2 − and •OH radicals, mediated oxidative degradation processes. I am wondering the fundamental differences between the pyro-catalysis and the others, the different generation rate of ROSs? How to understand their big difference in balancing the tooth whitening efficiency and biosafety?
Response: thanks a lot for this comment. As mentioned by the referee, the photocatalysis, piezo-catalysis and pyro-catalysis are achieved via reactive oxidative species such as •OH and •O2 -. However, the mechanisms of these catalytic effects have essential differences.

1) photo-catalysis
Photo-catalysis uses the semiconductor properties of photocatalysts to convert optical energy into chemical energy. The general mechanism of semiconductor-assisted photo-catalysis is represented in Figure R1, when light energy (photons) hit the semiconductor surface with energy equal to or higher than the bandgap energy.
Electrons from the valance band will get excited to the conduction band, leaving holes at the valance band. The holes at the valance band can react with water molecules, generating hydroxyl radicals, which have a strong oxidizing capability that is used to degrade organic matters [Catalysts, 2021, 11].  Figure R2c). Once the applied stress is relieved, the polarization will be restored and more polarization-bound charges will be generated.
As a result, space charges from the electrolyte will be adsorbed on the surface again, thereby leaving those charges with opposite polarity (to the adsorbed charges) in the electrolyte to participate in the reactions ( Figure R2d). In brief, redox reactions can be accomplished over piezoelectric materials through the polarization-mediated accumulation and release cycles of surface screening charges [Angewandte Chemie, 2022, 134]. All the three catalytic processes can release ROS and achieve tooth whitening, however, the shortages of photocatalysis and piezo-catalysis affect their applications in oral cleaning, as listed in Supplementary  The reason why pyro-catalysis does not cause damage to tooth enamel has been added to page 18 of the text. "…stains are removed from the tooth surface, and no damage was caused to the enamel owing to the gentle and continuous release of ROS (Fig. 6b). In contrast, enamel whitened with commercial tooth whitening gels showed significant and irreversible damage to the enamel due to the violent nature of the response caused by the dramatic release of ROS from high peroxide concentrations (Fig.   6c)." (3) Why BaTiO3? Why BaTiO3 nanowires? What are the major considerations for choosing a material for tooth whitening, among the available materials? What are the major factors affecting activity of pyro-catalysts? It is strange that the activity is not significantly affected by size of pyro-catalysts, although surface area (A) is an important parameter determining the surface charge.
Response: thank you for this comment. As teeth whitening materials are so important for oral health, they should be cautiously chosen. There are several factors that should be taken into consideration when we choose materials for pyro-catalysis tooth whitening: 1) The pyroelectric properties of the material, 2) the ability of the material to generate ROS, and 3) The biosafety of the material.

1) The pyroelectric properties of the material
In this work, tooth whitening is achieved via the pyro-catalytic effect of nanomaterials, so the selected materials must possess favorable pyroelectric properties.
BTO is a classical pyroelectric material that is sensitive to temperature changes.  [Advanced Materials, 2019, 31.] 2) The ability of the material to generate ROS  International, 2020, 46] 3) The biosafety of the material.
Most important of all, the material we choose must be innoxious and friendly to the human body. The application of BTO as a biomaterial has been widely studied for many years. The biocompatibility of BTO was claimed in several studies in vitro and in vivo.
The in vitro studies have been done using 4T1 breast cancer cells. The results show that BTO nanoparticles have no effect on cell growth, proliferation and differentiation. And the in vivo biocompatibility assessment confirmed that BTO was not translocated to any of the major organs such as liver, kidney, lung, spleen, the heart in the treated mice.

Fig.R9 In vitro piezocatalytic therapy of cancer cells. a) Schematic illustration of cellular level piezocatalytic therapy in vitro. b) Cell viabilities after treatment with T-BTO-Gel at varied
concentrations. c) Cell viabilities after exposed to US irradiation (*p < 0.05, **p < 0.01,***p <

0.001). d) Confocal fluorescence images of cancer cells after various treatments, including control group, Gel group, T-BTO-Gel group, Gel + US group and T-BTO-Gel + US group. Scale bar = 40
μm. [Advanced Materials, 2020, 32]. In summary, BTO exhibits promising pyroelectric properties, can release considerable ROS due to oral temperature fluctuations and has a high level of biosafety, making it an ideal tooth whitening agent.
We selected BTO nanowires for our experiments in order to obtain an improved pyroelectric catalytic performance. According to the results of simulations, nanowires are capable to generate a higher pyroelectric potential and therefore have a better ability to actuate the generation of ROS. BTO nanowires generate a pyroelectric potential as high as 28.2 V under the same conditions with a temperature fluctuation range of 36-56℃, much higher than that generated by nanoparticles. This has been added on page The pyroelectric potential generated by BTO nanomaterials with different morphologies was simulated by Comsol Multiphysics. The crystal polarization is set along z-axis, and the constitutive relation is described by where T0 is the initial temperature, D is the electric displacement vector, 0 is the permittivity of vacuum, r is the permittivity of BTO, Ps is the spontaneous polarization at T0 with a value of 0.25 C m -2 , p denotes the pyroelectric coefficient which is 210 μC m -2 K -1 , and E is the internal electric field. The other parameters used in this simulation are predefined parameters in Comsol Multiphysics. It can be seen from the results that the pyroelectric potential is distributed along the polar axis. The maximum pyroelectric potential was observed when the largest temperature variation was reached. The comparison of pyroelectric potentials generated by BTO nanomaterials with different morphologies reveals that the pyroelectric potential generated by BTO nanowires is significantly increased, and impressively, the BTO nanowires generated a pyroelectric potential of 28.2 V with a length of 5 μm in this simulation.
For nanoscale pyro-catalysts, the main factor affecting the pyro-catalytic performance is attributed to the pyroelectric property of the material. The effect of material size on the performance is not significant, which mainly stems from the size effect of ferroelectrics. The effects of depolarization in small particles have been explained in terms of a randomly oriented surface charge layer that begins to dominate the highly ordered ferroelectric interior as particle size decreases [Chemistry of Materials, 2002, 14]. And a consequence of nanostructuring ferroelectric materials is the appearance of a critical size limit, below which spontaneous polarization cannot be sustained in a ferroelectric material [Journal of Materials Chemistry C, 2013, 1] [Chemosphere, 2018, 199]. The pyroelectric potential (∅pyro), due to temperature changes (ΔT), is governed by: where p, l and ΔT are the pyroelectric coefficient, nanofiber length and temperature variation, ε0 is the vacuum permittivity (8.854 pF m -1 ), εr is the relative permittivity.
The reported p and εr of BTO are ~ 210 μC•cm -2 •K -1 and ~ 100. For a given ΔT of 5 ℃, the required length of nanowire is at least 1.6 μm. The SEM images revealed that the BTO nanowires used in this study are generally ~5 um in length and therefore have the ability to generate •OH and •O2 -. We have added this part of the analysis to the manuscript to refine our work, which can be found in page 12 "Thermodynamically, the potential for generating OH and O2needs to be at least ~1.7 V and 1.9 V, respectively. The pyroelectric potential (∅pyro) induced by temperature fluctuations (ΔT) can be governed by Eq. 6.
Response: thank you for this comment. The tooth whitening through ROSs has been used in the commercial tooth whitening gel for many years, the degradation processes and intermediates have been confirmed to be harmless to human body. In fact, to isatin 5-sulfonic acid and probably to anthranilic acid, the toxicity of these two compounds was also evaluated. AB74, isatin 5-sulfonic acid, anthranilic acid, and NaCl were shown to be nontoxic at the range of concentrations evaluated (0-100 mg/L for AB74, isatin 5-sulfonic acid and anthranilic acid; 0-3 g/L for NaCl).
Thus, we may conclude that the pyro-catalytic tooth whitening via ROS will not produce harmful intermediates.

REVIEWERS' COMMENTS
Reviewer #2 (Remarks to the Author): The work demonstrates the potential of pyro-catalysis for tooth whitening, I am satisfied with the responses and revisions by the authors, and the revised version can be accepted. Anyway, I am still concerning about the feasibility and safety of the pyrocatalytic technique for practical applications, which would require further considerations and investigations.
(1) In Fig 1a, the eating scenario is replaced by drinking in revised version, but this change obviously cannot prevent the pyro-catalysis induced degradation products from entering the digestive tract.
On the other hand, the market-available peroxide-dominant tooth whitening products are normally not used during feeding or intaking, and, the degradation product could be immediately spat out by the customers, avoiding the possible damage to human body. Based on the above comments, it would better find suitable practical application scenario where pyro-catalysis would work separately from regular daily activities.
(2)Advanced oxidation processes involving the oxidation reactions of organic compounds by oxidative radical species, such as •O2− and •OH, often produce unpredictable intermediates that may be harmful, even the original organic compound is totally not toxic. For example, a similar concern is especially serious for drinking water disinfection treatment, where the production of toxic disinfection byproducts is usually one of the major concerns about drinking water safety.
I hope the authors would make some frank comments on the above concerns in the final version.

REVIEWERS' COMMENTS
Reviewer #2 (Remarks to the Author): The work demonstrates the potential of pyro-catalysis for tooth whitening, I am satisfied with the responses and revisions by the authors, and the revised version can be accepted. Anyway, I am still concerning about the feasibility and safety of the pyrocatalytic technique for practical applications, which would require further considerations and investigations.
(1) In Fig 1a, the eating scenario is replaced by drinking in revised version, but this change obviously cannot prevent the pyro-catalysis induced degradation products from entering the digestive tract.
On the other hand, the market-available peroxide-dominant tooth whitening products are normally not used during feeding or intaking, and, the degradation product could be immediately spat out by the customers, avoiding the possible damage to human body. Based on the above comments, it would better find suitable practical application scenario where pyro-catalysis would work separately from regular daily activities.
Response: thank you for this suggestion. At beginning, we also concern the risk of degradation products and ferroelectric particles entering the digestive tract during the tooth whitening process. After consulting with dentists, our pyro-catalysis tooth whitening strategy is feasible because the stained teeth were covered by the whitening retainer, in turn degradation products can be prevented from entering the digestive tract. Moreover, the degradation products can be released be by rinsing mouth at the end of whitening, which reduces the risk of degradation products to human body.
(2) Advanced oxidation processes involving the oxidation reactions of organic compounds by oxidative radical species, such as •O2− and •OH, often produce unpredictable intermediates that may be harmful, even the original organic compound is totally not toxic. For example, a similar concern is especially serious for drinking water disinfection treatment, where the production of toxic disinfection byproducts is usually one of the major concerns about drinking water safety.
Response: thank you for this valuable comment. The structure of organic matter is very complex, so there are multiple reaction pathways in the mineralization to H2O and CO2, which will probably lead to some unpredictable intermediates. However, the amount of unpredictable intermediates is very limited, which were usually extremely scarce or even undetectable. While pyro-catalytic tooth whitening is an efficient and time-saving process, we believe that the production of unpredictable intermediates will be more scarce in this short time period. The dentists told us the possibility of harmful unpredictable intermediates should be much weaker than the market-available peroxidedominant tooth whitening products. For example, Indigo Carmine (a commonly used chromogen in food additives) is an essential element to form tooth stains, can be degraded by ROS, the degradation pathways of Indigo Carmine have been reported in detail [Materials Science in Semiconductor Processing 2020, 105.]. Indigo Carmine degradation was analyzed by analytical techniques, UPLC-PDA and HR-QTOF ESI/MS that helps to identify the degradation products, organic reactions (Hydroxylation, oxidation, methylation, decarboxylation, and desulfonation), and four pathways of Indigo Carmine in water. All the reaction intermediates that can be detected are NOT harmful to human body.

Fig. R1 Proposed degradation pathways of IC in water by visible light by Ni-BaMo3O10
photocatalyst. [Materials Science in Semiconductor Processing 2020, 105.]